Free Radical Halogenations

Most reactions are linear: reactants turn into products. Organic reactions are more like a choose-your-adventure game with many possible destinations.

Did you ever read a “choose-your-adventure” style book as a kid? It usually went something like this:

You discover a dinosaur in your backyard. If you go up and talk to it, skip to page 5. If you run away screaming, go to page 2.

Depending on your answer, you would either embark on a marvelous adventure… or end up as a majestic creature’s lunch. Even if you didn’t read this kind of book, most story-based video games work on the same principle – everything depends on which choices you make.

Most of the time, organic reactions appear pretty straightforward. They proceed from one step to the next. Reactions involving radicals are a little more unpredictable.

Unstable Energy

Free radicals are molecules that have one unpaired electrons. Unpaired electrons, especially on carbon atoms, are very unstable and extremely reactive. They can even steal a hydrogen atom from another molecule along with one of its electrons in order to safely contain all the electrons in bonding pairs.

Unpaired electrons can also cause carbon molecules to rearrange into more stable configurations, or they can recombine with other free radicals to form stable bonds.

Some of these outcomes are more likely than others, especially ones that involve more readily available reactants and more stable intermediates. The best way to map a reaction like this is to write out your own “choose your adventure” story for the reaction.

Step 1: Initiation

Because radicals are so unstable and high-energy, they have to be generated using extreme methods like high heat (written as “delta”) or ultraviolet radiation (represented with “hv”). Some molecules are more prone to breaking apart into radicals, like hydrogen peroxide (H2O2) and halogens like Br2 or Cl2 and can be used as initiators.

Radical reactions involving halogens are useful because many of them end with the addition of a halogen to a simple alkane chain. Alkanes with halogens attached are perfect starting materials for substitution reactions, making them very useful in organic chemistry.

This step is written something like this:

Step 2: Propagation

Once free radicals have entered the mix, things start to get a little crazy. The radical can “pluck” a hydrogen off of a neighboring molecule to stabilize the lone electron, but that leaves another radical on the other compound. This sets off a chain reaction, because every reaction in the propagation step leads to another radical. This can continue indefinitely.

Step 3: Termination

The termination step ends the chain reaction, either by the recombination of two radicals (rare because of how short-lived each radical is) or by the quenching of the reaction with a scavenger molecule like O2 that will react with any remaining radicals.

Decision Trees

Overall, the process looks something like this:

Depending on which molecule the radical reacts with, it can follow many potential paths. Most of those paths result in additional propagation – they continue the chain reaction by recycling the reactants. A few are termination steps – they end the chain reaction. A few lead to side products, and a few lead to the desired product.

Drawing out a “decision tree” like this makes sure that all possible reactions are accounted for and all side products are identified.

Determining Likely Products: Stability and Statistics

While a radical reaction will result in a mixture of products, some products are more likely than others. If there is a higher concentration of one reactant, it will be more likely to react. Because radicals are very short-lived, there is not a high concentration of them at any given time. That makes recombination reactions less likely.

Additionally, if there are multiple hydrogen atoms in the hydrocarbon that can be abstracted by a radical resulting in different products, more stable radicals will be longer-lived and therefore found in higher concentrations. Those radicals will go on to form products, making those products more common.

Double bonds and some other structures can stabilize radical intermediates. For more details as to how this affects the regiochemistry of the reaction, check out this lecture with Dr. Laurie Starkey.

With a few simple concepts in hand, radical halogenations will be no match for a spirit of adventure.